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FRACS Matthews > Breast > Flashcards

Breast Flashcards

1
Q

Which breast patients should undergo genetic testing?

A

**HIGH RISK INDIVIDUALS ** + assessment of risk with BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) (>10% chance of carrying a gene mutation)

  1. 3x 1st or 2nd degree relatives with on the same side of the family with breast or ovarian cancer
  2. 2x 1st or 2nd degree relatives on the same side of the family with breast or ovarian cancer AND one of the following
    * Breast cancer < 40 yo
    * Bilateral breast ca
    * Breast and ovarian ca in the same woman
    * Ashkenazi Jewish ancestry
    * Male breast cancer
  3. One 1st or 2nd degree relative diagnosed with breast cancer < 45yo + another 1st or 2nd degree relative on the same side of the family with bone or soft tissue sarcoma < 45yo
  4. Member of the family in which a high risk mutation has been identified
  5. Woman deemed to be at high risk of ovarian cancer
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2
Q

What are the contraindications to BCT?

A
  1. Patient factors
    - Patient preference
    - Strong family history or known mutation
    - Connective tissue disorder and therefore RT poorly tolerated
    - Prior breast radiotherapy
    - Pregnancy
  2. Disease factors
    - Large tumour size in relation to breast
    - Inflammatory breast cancer
    - Multicentric
    - Multifocal or diffuse disease
    - Involved margins whereby BCS cannot be acheived with accptable cosmesis
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3
Q

What are the indications for adjuvant radiotherapy following breast surgery?

A
  1. All breast conserving surgery
  2. Mastectomy
    - T4
    - Axillary LN involvement
    - T2/3 tumours with poor prognostic features (<50yo, triple neg, high grade, LVI, +ve margin)
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4
Q

What are the predictors of reccurence following BCT?

A

**1. Patient related **
- younger patient
- smaller breast
- family history of breast cancer

**2. Tumour related **
- histology (high grade, invasive lobular ca more likely to have incomplete excision)
- LVI (2x rate of recurrence if present)
- Extensive in situ component
- Possibly mutiple tumours (not proven)

**3. Treatment related **
Postive margins
- Risk falls if re excised
- Younger age makes risk higher
- LCIS or ADH at margin does not increase the risk
Adjuvant treatment
- Endocrine or chemotherapy w/o RTx ineffective at decreasing local recurrence

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5
Q

What are the indications and contraindications for sentinel lymph node biopsy?

A

Indications:
- T1/T2 with clinically negative axilla
- DCIS if performing Mx or suspicious features such as a large or palpable mass
- considered in T3 with clinically negative axilla

Contraindications:
- T4
- Clinically +ve nodes
- Axillary status does not affect adjuvant management (age (elderly), early ER+ve disease.

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6
Q

What is your subsequent management of a positive sentinel lymph node?

A

Options include subsequent axillary dissection versus axillary radiotherapy (if fit criteria for AMAROS)
- T1/2, unifocal, clinically node negative, 1-2 +ve sentinel LNs, BCS
- AMAROS showed no difference in DFS or OS, with slightly higher recurrence and more 2nd primaries in axillary RT. Higher lymphodema in ALND.

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7
Q

What factors are taken into account when deciding on adjuvant chemotherapy?

A
  1. Age
    - Younger woman have a greater benefit
    - No evidence of benefit greater than 70
  2. Tumour factors
    - T stage, grade and LVI
  3. Nodal status
    - Greater benefit with node positive
  4. ER status
    - Benefit same in ER+ve v. ER -ve for young woman
    - Greater benefit for ER-ve for 50-69yo
    - For luminal A features, good prognosis overall and so does not need chemo (providing no other high risk features)
  5. HER2 status
    - greater benefit if HER2 +ve
  6. Molecular classification
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8
Q

What are the indications for adjuvant chemotherapy post breast surgery?

A
  1. ER+ve
    - Age (young patients)
    - Adverse features (high grade/LVI)
    - >T2
    - N+ve (1-3LNs with low RS <12 had good outcomes, not requiring chemo
    - Molecular profile - luminal B and ER +ve, LN -ve with RS > 25
  2. HER2+ve
    - tumours > 1cm
    - N+ve
  3. Triple negative
    - tumours > 0.5cm
    - N+ve
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9
Q

What is the regime and timing for adjuvant chemotherapy?

A
  1. Regime
    Athracycline and taxane combination chemo
    - ACT -> doxorubicin and cyclophosphamide 2 weekly for 4 cycles followed by paclitaxel every 2 weeks for 4 cycles
  2. Timing
    Start within 4-6 weeks after definitive breast surgery
    Concomitant RT - chemo then RTx
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10
Q

What is the mechanism of action and side effect of athracycline based chemotherapy?

A

Epirubicin and adriamycin (doxorubicin)

MOA
Inhibit topoisomerase II enzyme, preventing supercolied DNA to relax and therefore blocking DNA transcription and replication

**Side effects **
- Cardiotoxicity and CCF (rare but serious complications)
- Acute myeloid leukaemia and myelodysplasia

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11
Q

What is the mechanism of action and side effect of taxanes?

A

Paclitaxel

Mechanism of action
- Antimicrotubule agent that inhibit microtubule reorganisation and disruption of mitosis

Side effects
- Neutrapenia

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12
Q

What is the mechanism of action and side effect of tamoxifen?

A

Selective oestrogen receptor modulator (SERM) - oestrogen antagonist
- given for 5 years to reduce risk of breast ca recurrence and death by 30-40%
- longer for high risk (>T3 or LN_+ve) for 10 days

Side effects
- Hot flushes, vaginal dryness/bleeding
- Associated with endometrial ca and DVT/PE

Contraindicated in pregnancy

Can be given after chemo to minimise toxicity
RT - given with or after RT

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13
Q

What is the mechanism of action and side effects of aromatase inhibitors?

A

1st line - anastrozole / letrozole
2nd line - exemestane

Competitive inhibition of aromatase enzyme, inhibiting conversion of androgen to oestrogen in peripheral tissues
Suitable in post menopausal woman with hormone receptor positve ca

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14
Q

What is the mechanism of action and side effect of herceptin (trastuzumab)?

A

MOA
Monoclonal antibody targeting cells that overexpress the HER2 protein to interrupt growth signal of cancer cells
Side effect
Risk of cardiotoxicity (LVEF must be > 45% and no symptomatic heart failure)

(note - must be 3+ on IHC or demonstarted on FISH)

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15
Q

What are the side effetcs of radiotherapy?

A

Acute skin toxicity with erythema and desquamation
Late skin toxicity with pigmentation, telangiectasia and fibrosis
Shoulder stiffness
Lymphodema
Pneumonitis
Oesophagitis, bone radionecorsis and brachial plexopathy
Soft tissue sarcoma

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16
Q

What is the mechanism of action of radiotherapy?

A

Ionizing radiation is used to kill malignant cells
X-ray beams pass through tissues, photons interact with tissue atoms, energy released damages DNA
Normal cells activate cell cycle checkpoints allowing DNA repair to occur, however malignant cells pass on damaged DNA to daughter cells leading to apoptosis

17
Q

What are the pillars of treatment for breast cancer during pregnancy?

A

Surgery
- Aim for 2nd trimester
- BCS not recommended in 1st trimester given delay in RTx
- Immediate breast reconstruction not recommended due to asymmetry and increased operating time
- ALNDx recommended (safety concerns with SLNBx ? altered lymphatics)

Radiotherapy
- contraindicated during pregnancy

Chemotherapy
- not recommended in the 1st trimester
- ACT thought to be safe in the 2nd and 3rd trimester
- Chemo needs to be stopped 3 weeks prior to delivery (avoid myelosuppresion and septic complications)

HER2
- contraindicated during pregnancy

Endocrine
- Tamoxifen associated with miscarriage and birth defects

Need to avoid breast feeding whilst on chemo, endocrine, trastuzumab

18
Q

Principles of managing breast cancer in the elderly

A

Ultimately a weigh up between severity of disease and severity of comorbities with varying treatment options with associated complications/side effects

Patient factors
- Comorbidities, performance status
Disease factors
- Extent of disease
- Receptor status and thus options for systemic therapy

Rx
- ER+ve (not candidate for surgery based on comorbidities or extent of disease) -> neoadjuvant endocrine therapy -> restage -> surgery if resectable and fit

Taxane based chemo is tolerated better (docetaxel and cyclophosphamide)
HER2+ve -> herceptin + taxane based chemo

19
Q

What is the pathophysiology of metastasis of breast cancer?

A
  1. Dissociation of cells from one another
    - Down regulation of E-cadherin and thus detachment of cells from primary tumour
  2. Degradation of basement membrane and interstitial connective tissue
    - MMPs implicated in tumour cell invasion to remodel insoluble components of BM and IM
    - release ECM sequestered GFs - overexpressed
  3. Changes in attachment of tumour cells to ECM proteins
    - loss of normal loss of adhesion induced apoptosis
  4. Locomotion
    - involves many family of receptors and signalling proteins
    - potentiated by tumour cell derived cytokines
  5. Vascular dissemination and homing of tumour cells
    - Tumour emboli - form into a clump
    - Adhesion to the endothelium and egress through the basement membrane
    - Proliferation, angiogenesis and evasion of host defences
20
Q

How do you manage lymphoedema?

A
  1. General measures
    - Self monitoring of lymphoedema with education re signs of infection
    - Skin hygiene and nail care
    - Avoid placing limb in gravity dependent position
    - Wear graded compression sleeves
    - Avoid medical procedures in affected limbs and maintain an ideal body weight
  2. Physiotherapy
    - Manual lymphatic drainage through use of massage to fil cutaenous lymphatic vessels to promote dilation and contractility of lymphatic conduits and recruit collateral pathways for flow
    - Limb exercise and weight training are benficial
    - Decongestive physiotherapy - 2 phases of treatment and maintenance
  3. Compression therapy
    - Initial multilayered low stretch compression and then maintenance with a fitted compression garmetnt
    - Intermittent pneumatic compression
  4. Surgery
    - last resort if failed medical mgmt, recurrent celluliti
    - Lymphatic vessels distal to obstrucion anastamosed to healthy lymphatics proximal to obstruction
    - Ablation or reductive procedures used after fat deposition and fibrosis
21
Q

What are the causes of lymphoedema?

A

Primary
- Congenital (<1yo)
- Praecox (1-35 yo)
- Tarda (>35 yo)

Secondary
- Malignancy and its treatment. Tumour compression with obstruction of lymphatics, infiltration into vessels, surgical lymphadenectomy, radiotherapy to LN basins.
- Infection.
Filariasis (most common cause worldwide) and recuurent cellilitis
- Trauma
Disruption of lymphatics
- Inflammatory arthrtis
RA or psoriatic arthris
- Obesity

22
Q

What are the different stages of lymphoedema?

A

International society of lymphology

Stage 0
- subclinical with swelling not evident despite impaired lymphatic drainage

Stage 1
- ACcumulation of fluid that subsides with 24h limb elevation.
- Soft pitting with no dermal fibrosis

Stage 2
Fails to resolve with 24hr of limb elevation. Dermal fibrosis is present

Stage 3
Elephantiasis with pitting being absent and trophic skin changes

23
Q

How is the severity of lympoedema classified?

A

Based on the girth dfference between arms

Mild - < 3cm
Moderate - 3-5cm
Severe - > 5cm

24
Q

What are the management principles of inflammatory breast cancer?

A

NACT
- Approach is based on receptor status.
- Based on hormone +ve (chemo rather than endocrine), HER+ve (trastuzumab +/- pertuzumab), triple -ve (chemo only)
- Response is based on resolution of skin changes and reduction in size of mass (if present)

Surgery
- CP/PR -> mastectomy/ALNDx + RTx
- NR -> radiation -> Mastectomy/ALNDx if resectable

Adjuvant therapy
- RT (BCS -> WBRT and to LN basin if stage 3 disease. Mx -> residual locoregional disease, T4 or N+ve regardless of response, consider in T3 with incomplete response and high risk features).
- Hormone +ve -> endocrine therapy
- HER2+ve -> CR could give trastuzuumab +/- pertuzumab for 1 year or noCR TDM1.
- Triple -ve -> CR -> no further chemo, no CR -> capecitabine

25
Q

What are some risk reducing methods for breast cancer?

A
  1. Modifiable RF
    - cease OCP and HRT
    - reduce EtOH
    - cease smoking
    - regular exercise and weight loss
  2. Screening
    - self examination
    - clinical breast examination
    - imaging - annual with US/mammo/MRI (issues with radiation with mammo)
    - ovarian screening - ca125 and transvaginal US (not recommended in guidelines though)
  3. Chemoprevention
    - tamoxifen - use in woman with moderately increased risk to reduce risk of breast cancer by 40% (limited use in BRCA1/2 as high rate of ER-ve
    - raloxifen - normalises bone turnoverwith better safety profile. Only for post menopausal woman.
  4. Prophylactic surgery
    - Bilateral mastectomy to reduce risk of breast cancer by >90%. Reconstruction can be immediate with either prosthesis or autologous (lat dorsi flap or TRAM flap)
    - Bilateral salpingo-oophorectomy - delay after child bearing and reduced risk of ovarian cancer by >80%. ALso may reduce breast cancer in pre-menopausal women.
26
Q

Which genes are tested for in high risk breast cancer patients?

A

BRCA 1 2
PALB2
CHEK2
TP53
STK11
PTEN
CDH1
ATM

27
Q

How do you classify benign breast disease?

A

Congenital abnormalities
- SUpernumery nipple
- Accessory breast tissue
- Amastia or athelia (complete regression of primary.bud)

Aberrations of normal breast development and involution (ANDI)
- fibroadenoma
- phyllodes tumour
- adenoma
- harmartoma

  • duct ectasia
  • intraductal papilloma
  • fibrocystic change
  • breast cyst
  • galactococele
  • sclerosing adenosis
  • radial scars and complex sclerosing lesions
  • atypical hyperplasia

Non-ANDI
- Breast infection
- Lipoma
- Fat necrosis
- Gynaecomastia

28
Q

What is the cause of granulomatous mastitis?

A

Cause is not fully understood. Thought to start from a infection with bacteria (Corynebacterium spp.) with ongoing uncontrolled inflammation even after the infection is gone.

29
Q

What are the management options for granulomatous mastitis?

A

Usually supportive treatment (pain relief) as resolves over 6-18 months
Requires drainage of any infection associated to control sepsis

First line: 6 weeks to 3 months of doxycycline (bacteriostatic, acting on cornynebacterium and reducing skin inflammation).

Second line: Steroids -> more potential side efftects

Third line: Immunosuppresants (methotrexate) - get rheumatology involved if using this treatment

Try to avoid surgery as this can make the inflammation much worse

30
Q

What is pagets disease?

A

This is intraepithelial adenocarcinoma of the nipple skin with > 85% of these cases associated with underlying malignancy, half of which are clinically undetectable.

31
Q

What is the pathophysiology of Pagets disease?

A

Derived from the epidermotrophic theory and transformation theory

Epidermotrophic -> Paget cells arise from underlying adenoca 2nd to migration of cells along the basement membrane of ducts to the epidermis of the nipple

Transformation -> Transformation of epidermal keratinocytes (Toker cells) within the nipple that represents epidermal carcinoma in situ. (this theory falling out of favour)

32
Q

What is the typical clinical presentation of Paget’s disease?

A

Scaly, raw, vesicular or ulcerated lesion that begins on the nipple and spreads to the areola.
- associated with pain, pruritis, and burning sensation
- bloody discharge may be present
- nipple retraction or destruction
- unilateral
- 50% of cases will have an underlying palpable mass
- 20% no mass, 10-15% no mass but mammographic evidence
- 25% no mass or mammographic evidence but has underlying DCIS

Dx
Benign - eczema, dermatitis (contact, radiation), nipple adenoma
Malignant - bowens disease, BCC, melanoma

33
Q

How is Pagets disease diagnosed?

A

Triple assessment
Full thickness punch biopsy of the nipple
- intra peithelial Paget cells (large, round pale cytoplasm, hyperchromatic nuclei with prominent nucleoli)
- can mimic malignant melnoma (specific stains and immunohistochemistry)
- Over espress HER2

34
Q

What is phyllodes tumour?

A

Firboepithelial tumour with a characteristic “leaf like” architecture which is capable of a wide range of biological behaviour.

Peak age of onest is 40-50
High grade tumours more common in elderly
Associated with Li Fraumeni syndrome

35
Q

What are the histological characteristics of Phyllodes tumour?

A

Grossly indistinguishable from fibroadenomas

Spectrum from resembling a benign fibroadenoma to high grade sarcoma

Leaf like architecture that consists of cleft like spaces containing papillary projections of epithelial lined stroma with varying degrees of hyperplasia and atypia.

Whether benign, borderline or malignant is based on stromal overgrowth, stromal cellular atypia, mitotic activity and margins (infiltrative)

36
Q

What is the clinical presentation of Phyllodes tumour?

A

Majority are a firm discrete mass that is similar to a fibroadenoma. The mass >3cm or rapid growth, raises suspicion of Phyllodes.

Can grow very large with overlying skin being translucent and shiny

37
Q

What are the management options for Phyllodes tumour?

A

Wide 1cm margins (if <1cm and is borderline or malignant, re excision)
Mastectomy needed if cant acheive negative margin

Adjuvant
- Radiotherapy - borderline or malignant but not benign unless adequate margins cannot be acheived
- Chemo reserved for highly selective fit pts with large and high risk recurrent -> need MDM discussion as per the sarcoma MDT

FRACS Matthews (10 decks)

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